The intramolecular variant of the inverse-electron demand Diels-Alder reaction between nitrosoalkenes and nucleophilic olefins will be investigated. In order to define the viability of this reaction for the synthesis of various natural products we plan to examine a wide range of model substrates whih embody important structural parameters. Since nitrosoalkenes have only fleeting existence as reactive intermediates we will study various methods of generation of nitrosoalkenes. We intend to systematically examine the following structural parameters: 1) length and complexity of the sidechain dienophile, 2) compatibility of substituents on the diene, and 3) stereochemistry of the ring fusion in the polycyclic products. The products of these intramolecular nitrosoalkene-olefin cycloadditions (INOC) are 1,2(6H)-4,5-dihydrooxazines, which have enormous potential for elaboration into a variety of molecular structures. The applicability of the INOC reaction to organic synthesis will be demonstrated by example. We propose to develop a flexible method for the synthesis of medium-sized rings using the INOC reaction to assemble heterolytic-fragmentation substrates. A synthetic approach to the alkaloid dendramine, and studies related to the powerful convulsant drug picrotoxinin are described in detail. Model studies will be undertaken to investigate the incorporation of additional rings into the INOC reaction and the attendant stereochemical problems. In each of these cases the INOC reaction offers the following features: 1) convergent assembly of the pre-cyclization substrate, 2) efficient and stereoselective formation of the carbon skeleton and 3) strategic placement of functionality for elaboration into the final product.